Research

Microbial pathogens claim the lives of millions of people worldwide each year, while millions more suffer from chronic infections. Increases in antibiotic resistance threaten to undermine already limited treatment options, highlighting an urgent need for new therapeutic approaches. I seek to uncover the fundamental immune mechanisms of pathogen restriction, with the ultimate goal of developing new vaccines and therapies against infectious diseases.

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How do intestinal granulomas restrict Yersinia infection?

Some infectious microbes have evolved to subvert host immunity, resulting in chronic disease. In these contexts, immune cells adopt an alternative strategy by surrounding and trapping the pathogens within granulomas, temporarily preventing further spread and organ damage. Although generally considered protective, these immune structures also provide a niche from which pathogens can spread should the immune system be compromised, the primary example being reactivation of tuberculosis in patients suffering from AIDS. Granulomas occur in a vast array of diseases from leishmaniasis, tuberculosis and histoplasmosis to Hodgkin’s lymphoma, sarcoidosis and Crohn’s disease. However, the molecular basis of pathogen restriction within these structures remains poorly defined. Yersinia pseudotuberculosis is a bacterial pathogen that colonizes the intestinal tract, causing gastroenteritis and triggering the formation of granulomas. In this study, we are exploring how intestinal granulomas are sterilized and cleared. Understanding this process may enable host-directed approaches to enhance immunity against pathogens that are resistant to antibiotics and alleviate granulomatous diseases.

How can we boost immunity to Pseudomonas infection?

Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen and a leading cause of hospital-acquired infections. It can establish both acute and chronic infections, particularly in vulnerable populations, such as patients with pneumonia, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). The World Health Organization has classified P. aeruginosa as a critical priority pathogen due to its increasing multidrug resistance, notably to front-line antibiotics like carbapenems, which severely limits treatment options and contributes to high morbidity and mortality rates. With traditional antibiotic therapies being increasingly ineffective, there is an urgent need for alternative treatment strategies. One promising approach to solve this problem is the development of host-directed therapies, which aim to enhance the immune system in its ability to contain or eliminate infection. Macrophages are central to the early innate immune response against Pseudomonas, but the bacterium has evolved numerous mechanisms to subvert their antimicrobial functions. By priming the cells with specific inflammatory mediators, we aim to reprogram their responses to improve bacterial clearance and identify signaling pathways that support host protection. This strategy may pave the way for novel therapeutic interventions that circumvent the limitations of antibiotic-based treatments.